Comparative genomics of the niche-specific plant pathogen Streptomyces ipomoeae reveal novel genome content and organization.

IMPORTANCE: While most plant-pathogenic Streptomyces species cause scab disease on a variety of plant hosts, Streptomyces ipomoeae is the sole causative agent of soil rot disease of sweet potato and closely related plant species. Here, genome sequencing of virulent and avirulent S. ipomoeae strains coupled with comparative genomic analyses has identified genome content and organization features unique to this streptomycete plant pathogen. The results here will enable future research into the mechanisms used by S. ipomoeae to cause disease and to persist in its niche environment.

Growth after implementing a donor breast milk program in neonates <33 weeks gestational age or birthweight <1500 grams: Retrospective cohort study.

BACKGROUND: Donor breast milk (DBM) feeding has been associated with less growth than formula in preterm infants. Zinc content in DBM is insufficient to support growth in preterm infants. OBJECTIVE: To compare growth from birth to discharge, macro- and micronutrient intake and the frequency of poor growth before (Epoch-1) and after (Epoch-2) implementing a DBM program. METHODS: Retrospective cohort study of 1069 infants born at < 33 weeks' gestational age or birthweight < 1500 g and fed using our adjustable feeding protocol with accurate serial length measurements. Growth was assessed by changes in Z-scores of weight, length and fronto-occipital circumference from birth to discharge. RESULTS: Growth did not decrease significantly in Epoch-2. However, energy and protein intake increased by 5% and frequency of zinc and vitamin D supplementation increased by >30%. CONCLUSIONS: DBM implementation did not significantly decrease growth from birth to discharge using our adjustable feeding protocol.

Tractographic and Microstructural Analysis of the Dentato-Rubro-Thalamo-Cortical Tracts in Children Using Diffusion MRI.

The dentato-rubro-thalamo-cortical tract (DRTC) is the main outflow pathway of the cerebellum, contributing to a finely balanced corticocerebellar loop involved in cognitive and sensorimotor functions. Damage to the DRTC has been implicated in cerebellar mutism syndrome seen in up to 25% of children after cerebellar tumor resection. Multi-shell diffusion MRI (dMRI) combined with quantitative constrained spherical deconvolution tractography and multi-compartment spherical mean technique modeling was used to explore the frontocerebellar connections and microstructural signature of the DRTC in 30 healthy children. The highest density of DRTC connections were to the precentral (M1) and superior frontal gyri (F1), and from cerebellar lobules I-IV and IX. The first evidence of a topographic organization of anterograde projections to the frontal cortex at the level of the superior cerebellar peduncle (SCP) is demonstrated, with streamlines terminating in F1 lying dorsomedially in the SCP compared to those terminating in M1. The orientation dispersion entropy of DRTC regions appears to exhibit greater contrast than that shown by fractional anisotropy. Analysis of a separate reproducibility cohort demonstrates good consistency in the dMRI metrics described. These novel anatomical insights into this well-studied pathway may prove to be of clinical relevance in the surgical resection of cerebellar tumors.

Mindfulness-Based Stress Reduction in the Management of Chronic Pain and Its Comorbid Depression.

CONTEXT: Chronic pain (CP) is a common and serious medical condition, with an estimated 100 million people affected in the United States. In the 1990s, opioids were increasingly prescribed to manage chronic pain, and this practice contributed to the opioid epidemic of the 21st century. To combat this epidemic, multidisciplinary approaches to chronic pain management are being researched and implemented. OBJECTIVE: To evaluate the clinical effectiveness of an 8-week mindfulness-based stress reduction (MBSR) course implemented in a semi-rural population with chronic pain. METHODS: Participants were recruited from a community-based teaching hospital in Corvallis, Oregon, for a pre-post study. Participants aged 34 to 77 years who reported having chronic pain lasting for at least 1 year before enrollment were included. Participants took an 8-week group MBSR course in 2.5-hour weekly sessions taught by an experienced MBSR instructor. Techniques were self-practiced between sessions with a goal of 30 minutes per day, 6 days per week. Pre- and postsurvey measurements of pain, depression, and functional capacity were taken via online surveys using the patient health questionnaire (PHQ-9), the Pain Catastrophizing Scale (PCS), and a shortened version of the Modified Oswestry Disability Index (MO). Participants were asked about their satisfaction with the program content, instructor, timing, and location. RESULTS: Twenty-eight participants were included in the study. Paired t tests found significant improvements in PHQ-9, PCS, and MO percent scores from before to after the course. PHQ-9 scores decreased by a mean of 3.7 points (95% CI, -5.5, -1.8), PCS scores decreased by a mean of 4.6 points (95% CI: -7.2, -2.0), and MO percent score decreased by a mean of 9.4% (95% CI: -14.2%, -4.6%). Results showed an overall downward shift in the distribution of depression, disability, and pain scores after the course. CONCLUSIONS: MBSR classes were found to benefit participants with chronic pain and depression in this setting, fostering significant improvement in participant perceptions of pain, mood, and functional capacity.

Mindfulness-Based Stress Reduction in the Management of Chronic Pain and Its Comorbid Depression.

Context: Chronic pain (CP) is a common and serious medical condition, with an estimated 100 million people affected in the United States. In the 1990s, opioids were increasingly prescribed to manage chronic pain, and this practice contributed to the opioid epidemic of the 21st century. To combat this epidemic, multidisciplinary approaches to chronic pain management are being researched and implemented. Objective: To evaluate the clinical effectiveness of an 8-week mindfulness-based stress reduction (MBSR) course implemented in a semi-rural population with chronic pain. Methods: Participants were recruited from a community-based teaching hospital in Corvallis, Oregon, for a pre-post study. Participants aged 34 to 77 years who reported having chronic pain lasting for at least 1 year before enrollment were included. Participants took an 8-week group MBSR course in 2.5-hour weekly sessions taught by an experienced MBSR instructor. Techniques were self-practiced between sessions with a goal of 30 minutes per day, 6 days per week. Pre- and postsurvey measurements of pain, depression, and functional capacity were taken via online surveys using the patient health questionnaire (PHQ-9), the Pain Catastrophizing Scale (PCS), and a shortened version of the Modified Oswestry Disability Index (MO). Participants were asked about their satisfaction with the program content, instructor, timing, and location. Results: Twenty-eight participants were included in the study. Paired t tests found significant improvements in PHQ-9, PCS, and MO percent scores from before to after the course. PHQ-9 scores decreased by a mean of 3.7 points (95% CI, -5.5, -1.8), PCS scores decreased by a mean of 4.6 points (95% CI: -7.2, -2.0), and MO percent score decreased by a mean of 9.4% (95% CI: -14.2%, -4.6%). Results showed an overall downward shift in the distribution of depression, disability, and pain scores after the course. Conclusions: MBSR classes were found to benefit participants with chronic pain and depression in this setting, fostering significant improvement in participant perceptions of pain, mood, and functional capacity.

Subcortical nuclei volumes are associated with cognition in children post-convulsive status epilepticus: Results at nine years follow-up.

PURPOSE: The purpose of the present study was to investigate the relationship between subcortical nuclei volume and cognition in children with post-convulsive status epilepticus (CSE). METHODS: Structural T1-weighted magnetic resonance imaging (MRI) scans (Siemens Avanto, 1.5 T) and neuropsychological assessments (full-scale intelligence quotient (FSIQ) and Global Memory Scores (GMS)) were collected from subjects at a mean 8.5 years post-CSE (prolonged febrile seizures (PFS), n = 30; symptomatic/known, n = 28; and other, n = 12) and from age- and sex-matched healthy controls (HC). Subjects with CSE were stratified into those with lower cognitive ability (LCA) (CSE+, n = 22) and those without (CSE-, n = 48). Quantitative volumetric analysis using Functional MRI of the Brain Software Library (FSL) (Analysis Group, FMRIB, Oxford) provided segmented MRI brain volumes. Univariate analysis of covariance (ANCOVA) was performed to compare subcortical nuclei volumes across subgroups. Multivariable linear regression was performed for each subcortical structure and for total subcortical volume (SCV) to identify significant predictors of LCA (FSIQ <85) while adjusting for etiology, age, socioeconomic status, sex, CSE duration, and intracranial volume (ICV); Bonferroni correction was applied for the analysis of individual subcortical nuclei. RESULTS: Seventy subjects (11.8 ±â€¯3.4 standard deviation (SD) years; 34 males) and 72 controls (12.1 ±â€¯3.0SD years; 29 males) underwent analysis. Significantly smaller volumes of the left thalamus, left caudate, right caudate, and SCV were found in subjects with CSE+ compared with HC, after adjustment for intracranial, gray matter (GM), or cortical/cerebellar volume. When compared with subjects with CSE-, subjects with CSE+ also had smaller volumes of the left thalamus, left pallidum, right pallidum, and SCV. Individual subcortical nuclei were not associated, but SCV was associated with FSIQ (p = 0.005) and GMS (p = 0.014). Intracranial volume and etiology were similarly predictive. CONCLUSIONS: Nine years post-CSE, SCV is significantly lower in children who have LCA compared with those that do not. However, in this cohort, we are unable to determine whether the relationship is independent of ICV or etiology. Future, larger scale studies may help tease this out.

Quantification of free sugars, fructan, pungency and sweetness indices in onion populations by FT-MIR spectroscopy.

BACKGROUND: To facilitate faster phenotyping of onions (Allium cepa L.), Fourier-transform mid infrared (FT-MIR) spectroscopy with partial least squares (PLS) regression modelling was evaluated for the determination of pungency (pyruvate), sweetness (free sugars) and fructan in juice samples (n = 605) expressed from bulbs from breeding populations. RESULTS: Fourier-transform infrared (FTIR) spectra (range 1700-900 cm-1 ) were obtained from droplets (30 µL) of unprocessed juice. Goodness-of-fit (r2 ) and prediction errors (standard error of cross validation) for optimal PLS models were: soluble solids (0.997, 0.1 °Brix), pyruvate [0.825, 0.8 µmol g-1 fresh weight (FW)], fructan (0.98, 1.9 mg g-1 FW), glucose (0.941, 1.1 mg g-1 FW), fructose (0.967, 1.0 mg g-1 FW) and sucrose (0.919, 1.7 mg g-1 FW). FTIR models for industry sweetness indices based on glucose or sucrose equivalents were also developed. Because of its very low concentration (0.8-12 µmol g-1 FW) relative to other compounds, pyruvate was the weakest model developed. Fructan could be determined spectroscopically without the need for enzymatic digestion. CONCLUSIONS: All of the chemometric models developed are acceptable for screening purposes. Those for soluble solids, fructan and fructose are also suitable for routine analysis. FT-MIR can therefore be utilised for the simultaneous determination of pungency, sweetness and fructan in this crop. © 2018 Society of Chemical Industry.

A six year head-to-head comparison of osteopathic and allopathic applicants to a university-based, allopathic general surgery residency.

OBJECTIVE: The number of osteopathic physicians is increasing as is the number applying to allopathic general surgery residency programs. A lack of knowledge of osteopathic schooling leads to a potential applicant bias in favor of allopathic applicants, but the 2 groups have not been compared head to head. DESIGN: Applications over a 6-year period to an allopathic general surgery residency program were reviewed. Demographics, examination scores, employment, education, and research experience were catalogued into a database. Allopathic applicants were compared with osteopathic applicants utilizing statistical analysis. SETTING: A university teaching hospital. PARTICIPANTS: Allopathic and osteopathic applicants to an allopathic general surgery residency program. RESULTS: A total of 1290 applications were reviewed; 1155 allopathic and 135 osteopathic applications. Other than race, the 2 cohorts are similar in age, gender, and citizenship. The groups are not significantly different with regard to the number of letter of recommendations, volunteer activities, scholarly works, and advanced degrees. Graduates of both proceed directly to residency. A significantly higher percentage of allopathic graduates reported their United States medical licensing examination (USMLE) scores, yet when osteopaths released their USMLE transcript, they scored significantly higher on the USMLE Step 1 examination and required fewer attempts to pass. These differences do not apply to the USMLE Step 2 examination. CONCLUSIONS: No single screening tool exists for selecting a successful general surgery resident. We are seeing increased numbers of osteopathic applicants. Many criteria used to evaluate applicants do not apply to osteopathic applicants, but our comparison of common selection variables on the Electronic Residency Application Service (ERAS) application did not demonstrate an overall difference. While our analysis demonstrated a statistically higher USMLE Step 1 score by osteopathic applicants, they may only self-report favorable data.

Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures.

OBJECTIVE: To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers. DESIGN: Double-blind, placebo-controlled clinical trial. SETTING: Academic medical centers. PARTICIPANTS: Subjects with mild to moderate Alzheimer disease. INTERVENTION: Random assignment to treatment for 16 weeks with 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q 3 times/d; or placebo. MAIN OUTCOME MEASURES: Changes from baseline to 16 weeks in CSF biomarkers related to Alzheimer disease and oxidative stress, cognition (Mini-Mental State Examination), and function (Alzheimer's Disease Cooperative Study Activities of Daily Living Scale). RESULTS: Seventy-eight subjects were randomized; 66 provided serial CSF specimens adequate for biochemical analyses. Study drugs were well tolerated, but accelerated decline in Mini-Mental State Examination scores occurred in the E/C/ALA group, a potential safety concern. Changes in CSF Aß42, tau, and P-tau(181) levels did not differ between the 3 groups. Cerebrospinal fluid F2-isoprostane levels, an oxidative stress biomarker, decreased on average by 19% from baseline to week 16 in the E/C/ALA group but were unchanged in the other groups. CONCLUSIONS: Antioxidants did not influence CSF biomarkers related to amyloid or tau pathology. Lowering of CSF F2-isoprostane levels in the E/C/ALA group suggests reduction of oxidative stress in the brain. However, this treatment raised the caution of faster cognitive decline, which would need careful assessment if longer-term clinical trials are conducted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00117403.

Herbal interventions for chronic asthma in adults and children: a systematic review and meta-analysis.

AIMS: To assess the efficacy of herb and plant extracts in the management of asthma. METHOD: Systematic review and meta-analysis. Multiple database searches identified randomised placebo controlled trials of herbal interventions reporting at least one primary outcome measure. Where possible data were combined for meta-analysis. Primary outcome measures were lung function, exacerbations and reduction in corticosteroid use. Secondary outcome measures were symptoms and symptom scores, use of reliever medications, changes in rates of consultation and adverse effects. RESULTS: Twenty-six studies reporting on 20 herbal preparations were included. Two of six studies reporting change in FEV1 were positive. Little data was available on frequency of exacerbations. For primary outcomes single studies of Boswellia, Mai-Men-Dong-Tang, Pycnogenol, Jia-Wei-Si-Jun-Zi-Tang and Tylophora indica showed potential to improve lung function, and a study of 1.8-Cineol (eucalyptol) showed reduced daily oral steroid dosage. CONCLUSIONS: Improvements in symptoms were not strongly supported by objective changes. Most trials were of small sample size, short duration, and poor methodology. Further adequately powered trials are needed to assess these compounds. Such trials should conform to CONSORT guidance, report standardised spirometry, and use validated symptom and severity scores. No recommendations for herbal treatment of asthma can be made from the current evidence.

EEG and MRI data fusion for early diagnosis of Alzheimer's disease.

The prevalence of Alzheimer's disease (AD) is rising alarmingly as the average age of our population increases. There is no treatment to halt or slow the pathology responsible for AD, however, new drugs are promising to reduce the rate of progression. On the other hand, the efficacy of these new medications critically depends on our ability to diagnose AD at the earliest stage. Currently AD is diagnosed through longitudinal clinical evaluations, which are available only at specialized dementia clinics, hence beyond financial and geographic reach of most patients. Automated diagnosis tools that can be made available to community hospitals would therefore be very beneficial. To that end, we have previously shown that the event related potentials obtained from different scalp locations can be effectively used for early diagnosis of AD using an ensemble of classifiers based decision fusion approach. In this study, we expand our data fusion approach to include MRI based measures of regional brain atrophy. Our initial results indicate that ERPs and MRI carry complementary information, and the combination of these heterogeneous data sources using a decision fusion approach can significantly improve diagnostic accuracy.

Disease-modifying therapies for Alzheimer disease: challenges to early intervention.

Prevention of Alzheimer disease (AD) is a national and global imperative. Therapy is optimally initiated when individuals are asymptomatic or exhibit mild cognitive impairment (MCI). Development of therapeutically beneficial compounds requires the creation of clinical trial methodologies for primary and secondary prevention. Populations in primary prevention trials selected only on the basis of age will have low rates of emergent MCI or AD. Epidemiologically based risk factors or biomarkers can be used to enrich trials and increase the likelihood of disease occurrence during the trial. Enrichment strategies for clinical trials with MCI include use of biomarkers such as amyloid imaging, MRI with demonstration of medial temporal lobe atrophy, bilateral parietal hypometabolism on PET, and reduced amyloid beta peptide and increased tau protein in CSF. Neuropsychological measures appropriate for trials of MCI may not be identical to those measures most suited for AD trials. Attention to these and other features of trial design, clinical assessment, and use of biomarkers is critical to improving the detection of disease-modifying effects of emerging therapies in presymptomatic or minimally symptomatic populations. The neurologic health of the growing aging population demands disease-modifying therapies and the development of methods to identify and test promising candidate agents.

Pectins from the albedo of immature lemon fruitlets have high water binding capacity.

The white part of citrus peel, the albedo, has a special role in water relations of both fruit and leaves from early on in fruit development. In times of drought, this tissue acts as a water reservoir for juice sacs, seeds and leaves. When water was injected into the albedo, free water was undetectable using magnetic resonance imaging. Microscopy showed tightly packed cells with little intercellular space, and thick cell walls. Cell wall material comprised 21% of the fresh albedo weight, and contained 26.1% galacturonic acid, the main constituent of pectin. From this, we postulated that pectin of the cell wall was responsible for the high water-binding capacity of the immature lemon albedo. Cell wall material was extracted using mild procedures that keep polymers intact, and four pectic fractions were recovered. Of these fractions, the SDS and chelator-soluble fractions showed viscosities ten and twenty times higher than laboratory-grade citrus pectin or the other albedo-derived pectins. The yield of these two pectins represented 28% of the cell walls and 62% of the galacturonic acid content of immature lemon albedo. We concluded that, from viscosity and abundance, these types of pectin account for the high water-binding capacity of this tissue. Compositional analyses showed that the two highly viscous pectic fractions differ in galacturonic acid content, degree of branching and length of side chains from the less viscous albedo-derived pectins. The most striking feature of these highly viscous pectins, however, was their high molecular weight distribution compared to the other pectic fractions.